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Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration

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Title Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration
 
Creator KARUNARATHNE, WKA
GIRI, L
PATEL, AK
VENKATESH, KV
GAUTAM, N
 
Subject optogenetics
ultrasensitivity
EUKARYOTIC CHEMOTAXIS
NEUTROPHIL CHEMOTAXIS
LOCAL-EXCITATION
RAC ACTIVATION
POLARIZATION
ULTRASENSITIVITY
DICTYOSTELIUM
INACTIVATION
SENSITIVITY
PI3K-GAMMA
 
Description There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune cell migration. Specific optical inputs to this optical trigger of signaling helped steer migration in all possible directions with precision. Spectrally selective imaging was used to monitor cell-wide phosphatidylinositol (3,4,5)-triphosphate (PIP3), cytoskeletal, and cellular dynamics. A switch-like PIP3 increase at the cell front and a decrease at the back were identified, underlying the decisive migratory response. Migration was initiated at the rapidly increasing switch stage of PIP3 dynamics. This result explains how a migratory cell filters background fluctuations in the intensity of an extracellular signal but responds by initiating directionally sensitive migration to a persistent signal gradient across the cell. A two-compartment computational model incorporating a localized activator that is antagonistic to a diffusible inhibitor was able to simulate the switch-like PIP3 response. It was also able simulate the slow dissipation of PIP3 on signal termination. The ability to independently apply similar signaling inputs to single cells detected two cell populations with distinct thresholds for migration initiation. Overall the optical approach here can be applied to understand G-protein-coupled receptor network control of other cell behaviors.
 
Publisher NATL ACAD SCIENCES
 
Date 2014-10-16T06:51:40Z
2014-10-16T06:51:40Z
2013
 
Type Article
 
Identifier PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(17)E1575-E1583
http://dx.doi.org/10.1073/pnas.1220755110
http://dspace.library.iitb.ac.in/jspui/handle/100/15480
 
Language en